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Cited by 547Gastrointestinal motility and disordersComplementary and Alternative Medicine StudiesDiet and metabolism studies

British Society of Gastroenterology guidelines on the management of irritable bowel syndrome

Open access
Vasant, Dipesh H, Paine, Peter A, Black, Christopher J, Houghton, Lesley A, Everitt, Hazel A, Corsetti, Maura, Agrawal, Anurag, Aziz, Imran +5 more·2021·Gut
DOI 10.1136/gutjnl-2021-324598
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Abstract

Irritable bowel syndrome (IBS) remains one of the most common gastrointestinal disorders seen by clinicians in both primary and secondary care. Since publication of the last British Society of Gastroenterology (BSG) guideline in 2007, substantial advances have been made in understanding its complex pathophysiology, resulting in its re-classification as a disorder of gut-brain interaction, rather than a functional gastrointestinal disorder. Moreover, there has been a considerable amount of new evidence published concerning the diagnosis, investigation and management of IBS. The primary aim of this guideline, commissioned by the BSG, is to review and summarise the current evidence to inform and guide clinical practice, by providing a practical framework for evidence-based management of patients. One of the strengths of this guideline is that the recommendations for treatment are based on evidence derived from a comprehensive search of the medical literature, which was used to inform an update of a series of trial-based and network meta-analyses assessing the efficacy of dietary, pharmacological and psychological therapies in treating IBS. Specific recommendations have been made according to the Grading of Recommendations Assessment, Development and Evaluation system, summarising both the strength of the recommendations and the overall quality of evidence. Finally, this guideline identifies novel treatments that are in development, as well as highlighting areas of unmet need for future research.

Integrity signals

Registry

Crossref · 10.1136/gutjnl-2021-324598

Cites

310 of 310 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

161 of 282 cited sources checked · 75 supported · 3 flagged · accuracy not yet measured

  • Interpretationreasoning

    The effect of FODMAP reintroduction to tolerance on IBS symptoms is unclear.

    “The effect of FODMAP reintroduction to tolerance on IBS symptoms is therefore unclear, although there have been open-label studies reporting the long-term efficacy of an adapted low FODMAP diet ranges somewhere between 50% and 60%.177 203”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [177] source

      The Introduction says evidence on reintroduction was previously unavailable, but this paper then studies it. Its Discussion reports that reintroduction to tolerance improved fiber intake without significant worsening of IBS symptoms; the Results report that reduced symptom severity was sustained at six months. Thus the paper does not present symptom outcomes after reintroduction as unclear. (LLM, conf=0.86)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites [203] O"Keeffe, 2018, Long-Term impact of the low-FODMAP diet on gastrointestinal symptoms, dietary intake, patient acceptability, and healthcare utilization in irritable bowel syndrome, Neurogastroenterol Motil source
  • Premisecitation

    Linaclotide 290 μg once a day ranked first across all end points, including abdominal bloating, in the network meta-analysis.

    “Linaclotide 290 μg once a day ranked first across all end points, including abdominal bloating (online supplemental figure 14-16 and online supplemental figure 19)”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [154] source

      The Results (p. 6) rank linaclotide 290 μg once daily first for the study’s efficacy endpoint, and the Discussion (p. 7) confirms that efficacy ranking. The Methods (p. 6) define that endpoint using abdominal pain and bowel movements; our copy does not report a ranking for abdominal bloating or establish that linaclotide ranked first across all endpoints. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [155] source

      The Discussion (p. 21) ranks linaclotide 290 μg once daily first for global symptoms, abdominal pain response, and complete spontaneous bowel movement response, but ranks tenapanor 50 mg twice daily first for bloating response. The Abstract (p. 7) makes the same distinction, contradicting the claim that linaclotide ranked first across all endpoints, including bloating. (LLM, conf=0.94)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Premisecitation

    Modulating activity of the brain regions responsible for visceral pain using various therapies has been shown to improve IBS symptomatology.

    “Modulating activity of the brain regions responsible for visceral pain using various therapies has been shown to improve IBS symptomatology.[36][37][38]”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [36] source

      The Background & Aims and Correlation of rCBF Changes and IBS Symptom Improvement sections report that alosetron improved IBS symptoms and that decreased activity in the amygdala, ventral striatum, and dorsal pons correlated with reduced abdominal pain. But the study tested one therapy and found reduced activity in central autonomic regions, not in areas activated by pain; it suggests rather than establishes that the brain changes caused the improvement. Page numbers were not available in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [37] source

      The Discussion reports that amitriptyline reduced pain-related brain activation during mental stress in patients with IBS, but describes symptom improvement through this mechanism as a postulate. The Symptom rating section found a nonsignificant preference for amitriptyline (p = 0.06) and a nonsignificant difference in pain ratings (p = 0.2). This single-drug study does not establish that various therapies improve IBS symptoms by modulating brain activity. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [38] source

      The Abstract and Conclusion report that cognitive therapy improved IBS symptoms alongside reduced activity in brain regions involved in pain perception. The paper studied one therapy and describes the neural changes as associated with improvement, not as proof that modulating those regions caused the improvement or that various therapies do so. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • Premisecitation

    The Rome IV criteria are potentially more specific than Rome III.

    “This feature makes the Rome IV criteria potentially more specific than Rome III.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [9] source

      In the IBS sensitivity analysis (page unavailable), the paper says Rome IV uses the more restrictive requirement of abdominal pain rather than Rome III’s abdominal pain or discomfort. It also estimates Rome IV specificity in a population survey, but the passages do not compare Rome IV and Rome III specificity, so they do not establish that Rome IV is more specific. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
  • Premisecitation

    Some patients with IBS have compromised central inhibitory regulation of visceral and somatic stimuli.

    “Some patients with IBS have compromised central inhibitory regulation of visceral and somatic stimuli.35”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [35] source

      The Discussion concludes that IBS patients showed compromised inhibitory regulation of somatic pain stimuli. It also reports an earlier finding of impaired inhibition during visceral stimulation, but cautions that distraction, hypervigilance, or peripheral gut sensitization could explain that finding; this paper therefore does not establish compromised central inhibition of visceral stimuli. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • May combine two claims. 121
  • Classified as probably not a substantial claim. 30

  • May combine two claims.

    Premisecitation

    Alosetron was withdrawn from the market in 2001 due to reports of ischaemic colitis. However, it was reintroduced in the USA via a risk evaluation and mitigation strategy, at a lower dose of 0.5 mg two times per day, for women with severe IBS-D.

    “Alosetron was withdrawn from the market in 2001 due to reports of ischaemic colitis. 234 However, it was reintroduced in the USA via a risk evaluation and mitigation strategy, at a lower dose of 0.5 mg two times per day, for women with severe IBS-D.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [234] source

      Split into 2 atoms — 0 confirmed, 1 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Symptoms in IBS are generated by interoceptive signals from the gut, and memories of such signals, and are modulated by emotional, cognitive and motivational factors.

    “Symptoms are generated by interoceptive signals from the gut, and memories of such signals, and are modulated by emotional (anxiety, depression), cognitive (attention, beliefs and expectation) and motivational factors.33”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    IBS is a disorder of altered bidirectional communication between the gut and brain via the gut-brain axis, and has a biopsychosocial aetiology.

    “IBS is a disorder of altered bidirectional communication between the gut and brain (via the gut-brain axis), and has a biopsychosocial aetiology.32”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Irritable bowel syndrome is a disorder of gut-brain interaction, rather than a functional gastrointestinal disorder.

    “resulting in its re-classification as a disorder of gut-brain interaction, rather than a functional gastrointestinal disorder.”
    • Also stated in: § CLASSIFICATION AND DIAGNOSTIC CRITERIA · plain
      “The Rome IV process also redefined IBS as a disorder of gut-brain interaction, in recognition of the complex interplay of biological, psychological, and social factors underpinning the condition.”
    • Also stated in: § PATHOPHYSIOLOGY · plain
      “As a result, it has been re-termed a disorder of gut-brain interaction.32”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [32] source

      The Special Issue Editors section says functional GI disorders are “better defined as Disorders of Gut-Brain Interaction,” supporting the terminology used for IBS. But its Table 1 still lists IBS under “Functional Gastrointestinal Disorders,” so the source does not support treating the two labels as mutually exclusive. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Interpretationcitation

    Reduced vagal tone may be caused by stress, and impacts on gut motility and sensitivity, and peripheral inflammation and gut permeability.

    “Reduced vagal tone may be caused by stress, and impacts on gut motility and sensitivity, and peripheral inflammation and gut permeability.40”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [40] Bonaz, 2018, The vagus nerve at the interface of the microbiota-gut-brain axis, Front Neurosci source

      The Introduction and “Stress, vagus nerve, and the microbiota” section say stress inhibits the vagus nerve and blunts its anti-inflammatory action. “Brain to gut interactions” says low vagal activity increases intestinal permeability and promotes systemic inflammation. The copy does not clearly establish the additional claim that reduced vagal tone affects gut motility and sensitivity. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Approximately 20% of patients with IBS are viscerally hyposensitive or insensitive to mechanical distension, more commonly those with IBS-C than IBS-D.

    “Approximately 20% of patients with IBS are viscerally hyposensitive or insensitive to mechanical distension, more commonly those with IBS-C than IBS-D, with one study suggesting that the degree of insensitivity correlated with abdominal distension (ie, a true physical increase in abdominal girth).43”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    Colonic transit time correlates inversely with stool consistency and, to a lesser extent, with stool frequency.

    “Colonic transit time correlates inversely with stool consistency and, to a lesser extent, with stool frequency.45”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    The severity and frequency of abdominal pain correlates with the presence of activated mast cells in close proximity to nerve endings in the gut mucosa in some studies, but in others mast cell proliferation associates with a reduction, or no change, in visceral sensitivity.

    “The severity and frequency of abdominal pain correlates with the presence of activated mast cells in close proximity to nerve endings in the gut mucosa in some studies, 56 but in others mast cell proliferation associates with a reduction, 57 or no change, 58 in visceral sensitivity.”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [56] source
    • cites [57] source
    • cites [58] source

  • May combine two claims.

    Premisecitation

    There is some evidence for epigenetic changes in IBS, including alterations in DNA methylation, and various miRNAs appear to be associated with increased visceral sensitivity and permeability.

    “There is some evidence for epigenetic changes in IBS, including alterations in DNA methylation, and various miRNAs appear to be associated with increased visceral sensitivity and permeability.80”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [80] Mahurkar-Joshi, 2020, Epigenetic mechanisms in irritable bowel syndrome, Front Psychiatry source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Lower gastrointestinal symptoms frequently prompt people to present to primary care, accounting for approximately 1 in 12 of all consultations.

    “Nevertheless, lower gastrointestinal symptoms frequently prompt people to present to primary care, 81 accounting for approximately 1 in 12 of all consultations.82”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [81] source

      Citation 82 is attached to the estimate that lower gastrointestinal symptoms account for approximately 1 in 12 primary-care consultations. The Discussion instead reports that IBS or IBS-related symptoms account for approximately 7.5% of outpatient attendances across all specialties; the Introduction describes a primary-care burden but gives no proportion of all primary-care consultations. Searches for the one-in-twelve estimate and a primary-care consultation percentage found no supporting passage. (LLM, conf=0.75)

      Experimental — accuracy not yet measured
    • cites [82] source

      The Discussion states that gastrointestinal problems account for about one in 12 primary-care consultations. The Screening and Demographics section likewise reports gastrointestinal complaints in 8.2% of screened patients. Neither passage limits that figure to lower gastrointestinal symptoms, so the claim is narrower than the source supports. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Abdominal distension correlates with oro-caecal and colonic transit times, and inversely with stool consistency.

    “whereas abdominal distension (the physical increase in abdominal girth, rather than the sensation of bloating) correlates with oro-caecal and colonic transit times, and inversely with stool consistency.46”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    In a mouse model, bacterial infection led to an increase in intestinal permeability, which appeared to allow previously tolerated food antigens to activate a localised host immune response in the gastrointestinal tract, via IgE, leading to histamine release, altered motility and visceral hypersensitivity.

    “In a mouse model, bacterial infection led to an increase in intestinal permeability, which appeared to allow previously tolerated food antigens to activate a localised host immune response in the gastrointestinal tract, via IgE, leading to histamine release, altered motility and visceral hypersensitivity.73”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [73] source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Changes in gastrointestinal motility may be influenced by alterations in serotonin metabolism, with high levels reported in patients with IBS-D, and low levels in IBS-C.

    “Changes in gastrointestinal motility may be influenced by alterations in serotonin (5-Hydroxytryptamine (5-HT)) metabolism, 49 with high levels reported in patients with IBS-D, and low levels in IBS-C.50”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [49] source
    • cites [50] source

  • May combine two claims.

    Premisecitation

    Functional gastrointestinal disorders, such as IBS, are by far the most common diagnosis, but symptoms can be difficult to assess and the possibility of colorectal cancer or inflammatory bowel disease (IBD) may create diagnostic uncertainty for clinicians, and anxiety for patients.

    “Functional gastrointestinal disorders, such as IBS, are by far the most common diagnosis, but symptoms can be difficult to assess and the possibility of colorectal cancer or inflammatory bowel disease (IBD) may create diagnostic uncertainty for clinicians, and anxiety for patients.83”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [83] source

      Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    General practitioners provide the majority of long-term medical care for people with IBS, referring only a minority of patients to specialist clinics.

    “General practitioners provide the majority of long-term medical care for people with IBS, referring only a minority of patients to specialist clinics.86”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [86] source

      The Methods (Description of CBT interventions and TAU; page unavailable) describe usual GP or consultant follow-up, supporting that GPs provide ongoing care for some patients with IBS. The paper does not establish that GPs provide the majority of long-term care or that only a minority of patients are referred to specialist clinics. (LLM, conf=0.83)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Interleukin-10 mRNA expression and protein levels are consistently reduced in the mucosa and/or peripheral circulation, in patients with IBS-D and PI-IBS, and associate with comorbid anxiety or depression.

    “Interleukin-10 mRNA expression and protein levels are consistently reduced in the mucosa and/or peripheral circulation, in patients with IBS-D and PI-IBS, and associate with comorbid anxiety or depression.59”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [59] source

      The Results sections comparing IBS-D patients with controls and comparing patients with and without anxiety-depression report lower IL-10 levels in blood and sigmoid colon mucosa. The Methods describe protein-level assays and immunohistochemistry, not mRNA measurement; the paper does not report findings for PI-IBS. No page numbers are available in our copy. (LLM, conf=0.90)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    FODMAPS may also trigger bowel symptoms as they produce short chain fatty acids, which lower colonic pH.

    “They may also trigger bowel symptoms as they produce short chain fatty acids, which lower colonic pH.202”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [202] Spiller, 2021, Impact of diet on symptoms of the irritable bowel syndrome, Nutrients source

      Section 5 links FODMAP fermentation to bowel symptoms and suggests that short-chain fatty acids could mediate mast-cell activation. But it attributes the fall in pH to accumulated lactate, not to short-chain fatty acids, so the claimed pH mechanism is not supported. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Patients reporting adverse food reactions experience more severe gastrointestinal symptoms, associated subjective health complaints of musculoskeletal pains and chronic fatigue and reduced quality of life, compared with those without food sensitivities.

    “Patients reporting adverse food reactions experience more severe gastrointestinal symptoms, associated subjective health complaints of musculoskeletal pains and chronic fatigue and reduced quality of life, compared with those without food sensitivities.[189][190][191]”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [189] source
    • cites [190] source
    • cites [191] source

      The Discussion reports that many patients with perceived food hypersensitivity had musculoskeletal pain and chronic fatigue in addition to IBS, and the Conclusions describe these as prevalent comorbidities. However, the study enrolled patients with perceived food hypersensitivity only; it does not establish that their symptoms were more severe, or their quality of life lower, than in people without food sensitivities. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Evidence suggests that 2 minutes of active listening at the beginning of a consultation gives the patient the feeling of having being listened to, and therefore having confidence in subsequent decisions around their care.

    “Evidence suggests that 2 minutes of active listening at the beginning of a consultation gives the patient the feeling of having being listened to, 109 and therefore having confidence in subsequent decisions around their care.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [109] source

      The Participants, methods, and results section reports that doctors used active-listening techniques and that 78% of patients finished their initial statement within two minutes. The paper does not report whether patients felt listened to or had greater confidence in subsequent care decisions; it measured talking time, not those perceptions. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    The diagnostic performance of alarm symptoms or signs is modest, and up to 80% of patients with IBS in primary and secondary care will report at least one alarm symptom.

    “although the diagnostic performance of alarm symptoms or signs is modest, 122 and up to 80% of patients with IBS in primary and secondary care will report at least one alarm symptom.123”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [122] source
    • cites [123] source

      The citation is attached to the prevalence claim, not the preceding statement about diagnostic performance. The Gastroenterologists vs. primary care section (p. 6) reports that 84.3% of patients with a clinical IBS diagnosis in the combined primary-care and gastroenterology sample reported a red flag. This supports the general point, but the reported figure exceeds the claimed 'up to 80%' bound. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    The yield of colonoscopy in patients with IBS is extremely low, and there is no evidence of reassurance being derived by patients from a normal examination.

    “The yield of colonoscopy in patients with IBS is extremely low, 125 and there is no evidence of reassurance being derived by patients from a normal examination.126”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [125] source

      The Discussion reports that colonoscopy did not alter the IBS diagnosis in 457 of 466 patients (98.1%), supporting the claim of low diagnostic yield. The study included patients with non-constipated IBS and no warning signs, so it does not establish the yield for all patients with IBS. The reassurance clause is attached to a different citation and is not assessed here. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [126] source

  • May combine two claims.

    Premisecitation

    FODMAPS increase small intestinal water volume and colonic gas production and, in those with visceral hypersensitivity, induce gastrointestinal symptoms.

    “They increase small intestinal water volume and colonic gas production and, in those with visceral hypersensitivity, induce gastrointestinal symptoms.201”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    Studies using small intestinal aspiration, considered the gold standard for diagnosing small intestinal bacterial overgrowth, have not demonstrated an increased prevalence of the condition in suspected IBS, and the lactulose breath test correlates poorly with small intestinal aspiration.

    “Studies using small intestinal aspiration, considered the gold standard for diagnosing small intestinal bacterial overgrowth, have not demonstrated an increased prevalence of the condition in suspected IBS, 143 and the lactulose breath test correlates poorly with small intestinal aspiration.144”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [143] source
    • cites [144] source

  • May combine two claims.

    Premisecitation

    IgG antibodies to yeast were reported in 87% of patients yet are rarely responsible for symptoms following dietary rechallenges.

    “For example, IgG antibodies to yeast were reported in 87% of patients yet are rarely responsible for symptoms following dietary rechallenges.195 196”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [195] source

      Table 2 (Discussion; page not provided) lists yeast among the foods excluded for 86.7% of the treatment group, consistent with the rounded 87% figure, but it does not establish that percentage for all patients. The Reintroduction of eliminated foods section reports symptoms after foods were reintroduced as a group; it does not report yeast-specific rechallenge results or say yeast was rarely responsible for symptoms. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [196] Hunter, 2005, Food elimination in IBS: the case for IgG testing remains doubtful, Gut

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    IBS is one of the most common disorders that gastroenterologists deal with, accounting for at least 10% of consultations in the outpatient clinic.

    “IBS is one of the most common disorders that gastroenterologists deal with, accounting for at least 10% of consultations in the outpatient clinic.105”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [105] source

      The Results report IBS in 62 of 613 patients (10.1%), and the Discussion identifies it as one of the commonest functional gastrointestinal disorders seen. The study counted consecutive new referrals to one luminal gastroenterology clinic, not all outpatient consultations, including follow-up visits. (LLM, conf=0.83)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Previous acute enteric infection is present in approximately 10% of people with IBS.

    “including previous acute enteric infection, present in approximately 10% of people with IBS, 112”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    The presence of bloating is not required to fulfil the Rome IV criteria but, if present, is highly suggestive of IBS, and is often accompanied by visible abdominal distension.

    “The presence of bloating is not required to fulfil the Rome IV criteria but, if present, is highly suggestive of IBS, and is often accompanied by visible abdominal distension.114”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [114] source

      The Results (p. 1) report greater bloating in IBS patients than controls and distention in 48% of patients; the Discussion (p. 7) notes that some IBS patients do not experience bloating. However, the study used Rome II criteria, not Rome IV, and does not establish that bloating is highly suggestive of IBS; seven of 20 healthy volunteers also reported bloating (p. 3). (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    The effect of fibre in IBS was limited to soluble fibre, such as ispaghula (RR 0.83; 95% CI 0.73 to 0.94), but not insoluble fibre, like wheat bran, which may exacerbate abdominal pain and bloating.

    “However, this effect was limited to soluble fibre, such as ispaghula (RR 0.83; 95% CI 0.73 to 0.94), but not insoluble fibre, like wheat bran, which may exacerbate abdominal pain and bloating.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [158] source

      The ‘Efficacy and Safety of Prebiotics in IBS’ section (page unavailable) discusses fructooligosaccharides and trans-galactooligosaccharides, not a comparison of soluble and insoluble fibre. Searches for ispaghula, wheat bran, soluble fibre, and the stated RR and confidence interval found no passage supporting the claim or its statement about worsened pain and bloating. (LLM, conf=0.77)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    An empathic approach can improve quality of life and symptoms, reduce healthcare visits and enhance adherence to treatment.

    “An empathic approach can improve quality of life and symptoms, 110 reduce healthcare visits and enhance adherence to treatment.108 111”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [108] source
    • cites [110] source

      The Discussion (page unavailable) says that helping patients make sense of their IBS could improve quality of life, and the paper links a mutually understanding doctor–patient relationship with maintaining quality of life. It does not report that an empathic approach improves symptoms, reduces healthcare visits, or increases treatment adherence; its exploratory findings also do not establish that the approach causes improvement. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [111] source

  • May combine two claims.

    Premisecitation

    There is some evidence from RCTs that regular exercise can be beneficial for IBS, particularly for constipation, with beneficial effects still apparent at 5 years in one trial.

    “All patients should be advised of the potential benefits of regular exercise, as there is some evidence from RCTs that this can be beneficial, 150 151 particularly for constipation, 150 with beneficial effects still apparent at 5 years in one trial.152”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites 150 151

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [150] source
    • cites [152] source

  • May combine two claims.

    Premisecitation

    Symptoms of BAD can mimic IBS-D, with between one-in-three and one-in-four patients with suspected IBS-D having an abnormal SeHCAT retention, and response rates to a bile acid sequestrant are higher at retentions of <10% or <5%.

    “Symptoms of BAD can mimic IBS-D, with between one-in-three and one-in-four patients with suspected IBS-D having an abnormal SeHCAT retention, 133 134 and response rates to a bile acid sequestrant are higher at retentions of <10% or <5%.135”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites 133 134

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [135] source

  • May combine two claims.

    Premisecitation

    Patients meeting the Rome IV criteria were 21 times more likely to have IBS-C than to not have IBS-C, and 11 times more likely to have IBS-M than to not have IBS-M after limited diagnostic workup.

    “Patients meeting these criteria were 21 times more likely to have IBS-C than to not have IBS-C, and 11 times more likely to have IBS-M than to not have IBS-M after limited diagnostic workup.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [21] source

      The Validation of the Rome IV Criteria for IBS section reports positive likelihood ratios of 25.7 for IBS with constipation and 10.6 for IBS with mixed bowel habits; the latter is approximately 11, but the former is not 21. The Introduction’s figure of 21 concerns IBS overall in an earlier validation study, not IBS-C in this study. The Investigative Work-up section describes a standardised but non-exhaustive work-up. (LLM, conf=0.89)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation

    Overall, adverse events with peppermint oil were no more common than placebo, although patients can report gastro-oesophageal reflux symptoms due to its effects on the lower oesophageal sphincter.

    “Overall, adverse events with peppermint oil were no more common than placebo, 160 although patients can report gastro-oesophageal reflux symptoms due to its effects on the lower oesophageal sphincter.”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Findingcitation

    Although loperamide improved stool frequency and consistency, it had no effect on global symptoms (RR 0.44; 95% CI 0.14 to 1.42).

    “Although the drug improved stool frequency and consistency, it had no effect on global symptoms (RR 0.44; 95% CI 0. 14 to 1 42).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [160] source

      The “9. Loperamide” section (page not available) reports no statistically significant improvement in overall IBS symptoms compared with placebo. It gives RR 0.42, not the claimed 0.44, and does not report improvement in stool frequency or consistency. A nonsignificant result also does not establish that loperamide had no effect. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Issues with following a low FODMAP diet, as opposed to traditional dietary advice, include the need for a specialist dietitian to implement it, followed by close monitoring to avoid nutritional deficiencies or the development of overly restrictive eating habits.

    “Issues with following a low FODMAP diet, as opposed to traditional dietary advice, include the need for a specialist dietitian to implement it, followed by close monitoring to avoid nutritional deficiencies or the development of overly restrictive eating habits.[207][208][209]”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [207] source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [208] Wilson, 2020, Challenges of the low FODMAP diet for managing irritable bowel syndrome and approaches to their minimisation and mitigation, Proc Nutr Soc source
    • cites [209] source

  • May combine two claims.

    Findingcitation

    Neither alverine nor mebeverine demonstrated benefit over placebo in this meta-analysis.

    “In contrast, in this meta-analysis, neither alverine nor mebeverine demonstrated benefit over placebo.”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Findingcitation

    Although both stimulant and osmotic laxatives are efficacious in the treatment of chronic idiopathic constipation, only the latter have been evaluated in 2 RCTs of polyethylene glycol, recruiting 181 patients with IBS-C.

    “Although both stimulant and osmotic laxatives are efficacious in the treatment of chronic idiopathic constipation, 220 only the latter have been evaluated in 2 RCTs of polyethylene glycol, recruiting 181 patients with IBS-C.221 222”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [220] source
    • cites [221] source
    • cites [222] source

  • May combine two claims.

    Findingcitation

    In a network meta-analysis, for global symptoms, peppermint oil was ranked first and antispasmodics third, with both superior to placebo.

    “Comparison of peppermint oil and antispasmodics with other unlicensed or 'traditional' treatments for IBS, including ispaghula and gutbrain neuromodulators, in a network meta-analysis suggested that, for global symptoms, peppermint oil was ranked first and antispasmodics third, with both superior to placebo (online supplemental figure 6).157”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    Preliminary data suggest that response to a low FODMAP diet may be predicted from baseline faecal bacterial profile and metabolomic activity, while a gluten-free diet may benefit those with serum antigliadin antibodies.

    “Preliminary data suggest that response to a low FODMAP diet may be predicted from baseline faecal bacterial profile and metabolomic activity, while a gluten-free diet may benefit those with serum antigliadin antibodies.[213][214][215]”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [213] source
    • cites [214] source
    • cites [215] Pinto-Sanchez MI , Nardelli A , Borojevic R , et al . Gluten-Free Diet Reduces Symptoms, Particularly Diarrhea, in Patients With Irritable Bowel Syndrome and Antigliadin IgG. Clinical Gastroenterology and Hepatology 2020;150.doi:10.1016/j.cgh.2020.08.040 source

  • May combine two claims.

    Findingcitation

    We updated a prior meta-analysis of 37 RCTs, incorporating data from 8 new trials and randomising 6352 patients.

    “We updated a prior meta-analysis of 37 RCTs, 158 incorporating data from 8 new trials [166][167][168][169][170][171][172][173] and randomising 6352 patients.”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [158] source
    • cites [166] Barraza-Ortiz, 2020, Combination of a probiotic and an antispasmodic increases quality of life and reduces symptoms in patients with irritable bowel syndrome: a pilot study, Dig Dis source
    • cites [167] source

  • May combine two claims.

    Findingcitation

    The overall rates of adverse events were significantly higher with antispasmodics compared with placebo; most notably dry mouth, visual disturbance and dizziness.

    “The overall rates of adverse events were significantly higher with antispasmodics compared with placebo; most notably dry mouth, visual disturbance and dizziness.160”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Findingcitation

    The prior systematic review and meta-analysis identified only 2 RCTs, comprising 111 participants, and noted that although a gluten-free diet was associated with a reduction in global symptoms compared with a control diet, this was not statistically significant (RR 0.42; 95% CI 0.11 to 1.55).

    “The prior systematic review and meta-analysis identified only 2RCTs, 161 comprising 111 participants and noted that although a gluten-free diet was associated with a reduction in global symptoms compared with a control diet, this was not statistically significant (RR 0.42; 95% CI 0. 11 to 1 55).”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Findingcitation

    In terms of effect on abdominal pain, antispasmodics ranked second, with peppermint oil third, and both were significantly more efficacious than placebo.

    “In terms of effect on abdominal pain, antispasmodics ranked second, with peppermint oil third (online supplemental figure 7).Again, both were significantly more efficacious than placebo.”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Findingcitation

    Adverse events included constipation, nausea and headache, and adverse events leading to drop out were significantly higher with active drug than placebo.

    “Adverse events included constipation, nausea and headache, and adverse events leading to drop out were significantly higher with active drug than placebo.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [153] source

      The Outcome assessment section (page unavailable) lists constipation, nausea and headache among the individual adverse events assessed. The Safety section (page unavailable) reports significantly more adverse-event-related dropouts than placebo for both studied doses of eluxadoline and for alosetron 1 mg twice daily, but not for active drugs generally. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation

    Pregabalin improved visceral hypersensitivity in one small trial, and in a recent RCT recruiting 85 patients with IBS, 12 weeks of pregabalin 225 mg twice daily led to significant improvements in global symptoms, abdominal pain, diarrhoea and bloating versus placebo.

    “Pregabalin improved visceral hypersensitivity in one small trial, 227 and in a recent RCT recruiting 85 patients with IBS, 12 weeks of pregabalin 225 mg twice daily led to significant improvements in global symptoms, abdominal pain, diarrhoea and bloating versus placebo.228”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [227] source
    • cites [228] source

  • May combine two claims.

    Findingcitation

    In contrast, SSRIs were ranked fifth and fourth for global symptoms and abdominal pain, respectively, and pregabalin was ranked sixth for global symptoms, with no benefit of either over placebo in these trials.

    “In contrast, SSRIs were ranked fifth and fourth for global symptoms and abdominal pain, respectively, and pregabalin was ranked sixth for global symptoms, with no benefit of either over placebo in these trials.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [157] source

      The Results on global IBS symptoms (p. 18) and abdominal pain (p. 19) identify only peppermint oil, TCAs, and antispasmodic drugs as significantly more effective than placebo, supporting the statement that SSRIs and pregabalin showed no demonstrated benefit on the relevant endpoints. The passages in our copy do not give the claimed fifth, fourth, and sixth rankings, so those precise ranks remain unsupported. (LLM, conf=0.80)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation

    In a previous meta-analysis, both alosetron 1 mg two times per day and ramosetron 2.5 μg or 5 μg once a day were superior to placebo across various end points, including the FDA composite end point for IBS-D (3 RCTs of alosetron 1 mg two times per day, 787 patients, RR 0.69; 95% CI 0.60 to 0.80, and 1 RCT of ramosetron 2.5 μg once a day, 348 patients, RR 0.78; 95% CI 0.67 to 0.91).

    “In a previous metaanalysis, 153 both alosetron 1 mg two times per day and ramosetron 2.5 μg or 5 μg once a day were superior to placebo across various end points, including the FDA composite end point for IBS-D (3 RCTs of alosetron 1 mg two times per day, 787 patients, RR 0.69; 95% CI 0.60 to 0.80, and 1 RCT of ramosetron 2.5 μg once a day, 348 patients, RR 0.78; 95% CI 0.67 to 0.91) (online supp”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [153] source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation

    In a meta-analysis of 12 RCTs of TCAs, recruiting 787 patients, these drugs were superior to placebo for global symptoms or abdominal pain (RR 0.65; 95% CI 0.55 to 0.77), and for abdominal pain alone (RR 0.59; 95% CI 0.42 to 0.83).

    “In a metaanalysis of 12 RCTs of TCAs, recruiting 787 patients, these drugs were superior to placebo for global symptoms or abdominal pain (RR 0.65; 95% CI 0.55 to 0.77) (online supplemental figure 8), and for abdominal pain alone (RR 0.59; 95% CI 0.42 to 0.83) (online supplemental figure 9).159”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Findingcitation

    Both alosetron and ramosetron were also more efficacious than placebo for global symptoms, abdominal pain and stool consistency.

    “Both drugs were also more efficacious than placebo for global symptoms, abdominal pain and stool consistency (online supplemental figures 11-13).”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Findingcitation

    SSRIs were also more efficacious for global symptoms or abdominal pain (RR 0.68; 95% CI 0.51 to 0.91), but not abdominal pain alone, and there was significant heterogeneity among the 7 trials, which contained only 356 patients.

    “SSRIs were also more efficacious for global symptoms or abdominal pain (RR 0.68; 95% CI 0.51 to 0.91) (online supplemental figure 8), but not abdominal pain alone (online supplemental figure 9), and there was significant heterogeneity among the 7 trials, which contained only 356 patients.159”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Findingcitation

    A network meta-analysis comparing the relative efficacy of all these licensed therapies for IBS-D demonstrated that alosetron 1 mg two times per day ranked first for the FDA composite end point for IBS-D and global symptoms, with ramosetron 2.5 μg once a day second.

    “A network meta-analysis comparing the relative efficacy of all these licensed therapies for IBS-D, across various end points, 153 demonstrated that alosetron 1 mg two times per day ranked first for the FDA composite end point for IBS-D and global symptoms (online supplemental figures 10 and 11), with ramosetron 2.5 μg once a day second.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [153] source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Eluxadoline is a μ-opioid and κ-opioid receptor agonist and δ-opioid receptor antagonist licensed for IBS-D. The drug slows intestinal transit and reduces visceral hypersensitivity.

    “Eluxadoline is a μ-opioid and κ-opioid receptor agonist and δ-opioid receptor antagonist licensed for IBS-D. The drug slows intestinal transit and reduces visceral hypersensitivity. 229”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [229] source

      The Background (Mechanism of action; page unavailable) confirms eluxadoline’s receptor profile and approval for IBS-D. The Background (Development; page unavailable) reports normalized GI transit in mice, consistent with slowing transit toward baseline. The paper discusses a rationale for effects on visceral sensation, but does not establish that eluxadoline reduces visceral hypersensitivity. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation

    In a network meta-analysis, TCAs were ranked second and first for their effect on global symptoms and abdominal pain respectively, and were more efficacious than placebo.

    “In a network meta-analysis evaluating relative efficacy of gutbrain modulators with other unlicensed or 'traditional' treatments, 157 TCAs were ranked second and first for their effect on global symptoms and abdominal pain respectively, and were more efficacious than placebo (online supplemental figures 6 and 7).”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Findingcitation

    For stool consistency alosetron 1 mg two times per day ranked first, with ramosetron 5 μg once a day second.

    “Finally, for stool consistency alosetron 1 mg two times per day ranked first, with ramosetron 5 μg once a day second (online supplemental figure 12).”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    Ramosetron is only available in Asia. There have been no reports of ischaemic colitis associated with the drug.

    “Ramosetron is only available in Asia. 153 There have been no reports of ischaemic colitis associated with the drug.”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • May combine two claims.

    Findingcitation

    Adverse events included constipation, nausea and headache; patients assigned to both drugs were more likely to report adverse events than with placebo.

    “Adverse events included constipation, nausea and headache; patients assigned to both drugs were more likely to report adverse events than with placebo.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [153] source

      The Safety section (page unavailable) reports significantly more overall adverse events with alosetron 1 mg twice daily and ramosetron 2.5 µg once daily than with placebo. The Discussion identifies constipation as an adverse event, but our copy does not identify nausea or headache among the reported events. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Adverse events were significantly more common with linaclotide 290 μg once a day, with diarrhoea being the most common.

    “Adverse events were signifi- cantly more common with linaclotide 290 μg once a day, with diarrhoea being the most common.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [155] source

      The Safety section (p. 19) reports significantly more overall adverse events with linaclotide 290 μg once daily than with placebo (RR 1.12; 95% CI 1.04–1.21). The adverse-event discussion (p. 20) reports an increased risk of diarrhea with linaclotide, but does not establish that diarrhea was its most common adverse event. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation

    Adverse event rates were significantly higher among patients treated with TCAs or SSRIs, with drowsiness and dry mouth the most common.

    “Adverse event rates were significantly higher among patients treated with TCAs or SSRIs, with drowsiness and dry mouth the most common.159”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [159] source

      The “Adverse Events with Antidepressant Therapy” section reports significantly more adverse events with antidepressants overall and with TCAs specifically. It says drowsiness and dry mouth were more common with TCAs than placebo, but does not establish a significantly higher adverse-event rate for SSRIs separately or identify those effects as the most common across both drug classes. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation

    In a meta-analysis of 2 RCTs, which recruited 1260 patients, rifaximin 550 mg three times a day for 14 days was more efficacious than placebo for the FDA composite end point for IBS-D (RR 0.92; 95% CI 0.86 to 0.98) and for stool consistency alone, but not for global symptoms or abdominal pain.

    “In a meta-analysis of 2 RCTs, 153 which recruited 1260 patients, rifaximin 550 mg three times a day for 14 days was more efficacious than placebo for the FDA composite end point for IBS-D (RR 0.92; 95% CI 0.86 to 0.98) (online supplemental figure 10) and for stool consistency alone (online supplemental figure 12), but not for global symptoms or abdominal pain (online supple- mental figures 11 and”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [153] source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Drugs acting as antagonists at the 5-HT3 receptor are also licensed for IBS-D. These include alosetron and ramosetron, which slow gastrointestinal transit, reduce visceral hypersensitivity and alter rectal compliance.

    “Drugs acting as antagonists at the 5-HT 3 receptor are also licensed for IBS-D. These include alosetron and ramosetron, which slow gastrointestinal transit, reduce visceral hypersensitivity and alter rectal compliance. [231][232][233]”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [231] source

      The Summary reports that alosetron delayed colonic transit in IBS patients and healthy volunteers. It also describes reduced rectal sensitivity with granisetron, increased rectal compliance with ondansetron, and increased colonic—not rectal—compliance with alosetron. The paper does not establish that alosetron or ramosetron was licensed for IBS-D, or report these effects for ramosetron; the Discussion instead calls alosetron a suitable treatment candidate. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [232] source
    • cites [233] source

  • May combine two claims.

    Findingcitation

    Headache was the most common adverse event, but side effects were no more common with rifaximin than with placebo.

    “Headache was the most common adverse event, but side effects were no more common with rifaximin than with placebo.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [153] source

      The Safety section (page unavailable) reports that rifaximin ranked best for overall adverse events and does not identify a significant increase versus placebo. The Outcome assessment section lists headache among the adverse events assessed, but our copy does not say it was the most common. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In the largest trial of CBT for IBS to date, at least 50% of patients met cutoffs for probable common mental disorders at baseline, and both therapist-delivered CBT over the telephone and web-based CBT using IBS-specific protocols reduced anxiety and depression scores at all follow-up points.

    “in the largest trial of CBT for IBS conducted to date at least 50% of patients met cutoffs for probable common mental disorders at baseline, and both therapist-delivered CBT over the telephone and web-based CBT using IBS-specific protocols reduced anxiety and depression scores at all follow-up points.86”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [86] source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Prucalopride is efficacious in the treatment of chronic idiopathic constipation, but to date there have been no RCTs in IBS-C.

    “Although prucalopride, which is a highly selective 5-HT 4 agonist with no known cardiovascular or cerebrovascular safety concerns, is efficacious in the treatment of chronic idiopathic constipation, 220 to date there have been no RCTs in IBS-C.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [220] source

      The Response to therapy with prucalopride section reports better outcomes than placebo in chronic idiopathic constipation, supporting efficacy. The paper reviews trials in that condition but does not establish the separate claim that no prucalopride RCTs had been conducted in IBS-C; a search for IBS-C trials found no passage addressing it. Page numbers were not available in our copy. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premiseown data

    Analysis of trials that only included patients with refractory symptoms reduced heterogeneity, and still demonstrated efficacy for CBT in some formats.

    “Analysis of trials that only included patients with refractory symptoms reduced the heterogeneity, and still demonstrated efficacy for CBT in some formats (online supple- mental figure 21).”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    A meta-analysis of 6 RCTs (639 patients) reported a RR of remaining symptomatic of 0.73 (95% CI 0.55 to 0.97) compared with education and/or support and 0.67 (95% CI 0.49 to 0.91) compared with a waiting list control for gut-directed hypnotherapy.

    “a meta-analysis of 6 RCTs, recruiting 639 patients, reported a RR of remaining symptomatic of 0.73 (95% CI 0.55 to 0.97) compared with education and/or support and 0.67 (95% CI 0.49 to 0.91) compared with a waiting list control (online supplemental figure 20).156”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [156] source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premiseown data

    Adverse events were significantly more frequent with plecanatide 3 μg once a day compared with placebo, and diarrhoea was significantly more likely with both doses.

    “Adverse events were significantly more frequent with plecanatide 3 μg once a day, compared with placebo, and diarrhoea was significantly more likely with both doses.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [155] source

      The Safety section (p. 19) reports significantly more overall adverse events with plecanatide 3 mg once daily than with placebo. It also reports that both plecanatide doses were significantly more likely to cause diarrhea than placebo (p. 20). The claim gives the 3 mg dose as 3 μg, a 1,000-fold difference. (LLM, conf=0.90)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based).

    Premisecitation

    Tenapanor 50 mg two times per day was more efficacious than placebo for an increase of ≥1 CSBMs per week from baseline in IBS-C.

    “and an increase of ≥1 CSBMs per week from baseline (online supplemental figure 16).”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    Early reports of clinical outcomes via videoconsultation are promising, with similar response rates achieved compared with face-to-face treatment.

    “Early reports of clinical outcomes via videoconsultation are also promising, with similar response rates achieved, compared with face-to-face treatment.259”
    Quote in the paperNot a substantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    Intervention with gut-focused hypnotherapy has been shown to have wider socioeconomic benefits including improving general well-being, reductions in healthcare utilisation in both primary and secondary care, reduced presenteeism at work, improved quality of life and long-term beneficial effects on symptoms.

    “However, intervention with gut-focused hypnotherapy has been shown to have wider socioeconomic benefits including improving general well-being, reductions in healthcare utilisation in both primary and secondary care, [254][255][256] reduced presenteeism at work, 255 improved quality of life 252 257 and long-term beneficial effects on symptoms, 256”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [254] source
    • cites [255] Houghton, 1996, Symptomatology, quality of life and economic features of irritable bowel syndrome--the effect of hypnotherapy, Aliment Pharmacol Ther source
    • cites [256] source

  • May combine two claims.

    Premisecitation

    IBS research is leading the way in this regard with the first UK interventional virtual trial being conducted in IBS, demonstrating that virtual recruitment methods outperform site-dependent recruitment significantly.

    “IBS research is leading the way in this regard with the first UK interventional virtual trial being conducted in IBS, demonstrating that virtual recruitment methods outperform site-dependent recruitment significantly.295 299”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [295] Kemppinen, 2020, Randomised, double-blind, placebo controlled multi-centre study to assess the efficacy, tolerability and safety of Enterosgel® in the treatment of irritable bowel syndrome with diarrhoea (IBS-D) in adults, Trials source

      The Methods/design > Recruitment section describes an IBS-D interventional trial in England that uses a website and registry alongside recruitment through approximately 30 clinical sites (page not specified). It does not identify the study as the first UK interventional virtual trial or report a comparison showing that virtual recruitment significantly outperformed site-dependent recruitment. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [299] Virtual trial recruits 67% faster led by NIHR Patient Recruitment Centre in Newcastle in collaboration with Enteromed, 2020. Available: https://www.nihr.ac.uk/news/virtual-trial-recruits-67-faster-led-by-nihr-patient-recruitment-centre-in-newcastle-in-collaboration-with-enteromed/26290

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Minesapride was well tolerated, with diarrhoea the most common side effect, and there were no cardiovascular adverse events.

    “The drug was welltolerated, with diarrhoea the most common side effect, and there were no cardiovascular adverse events.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [179] source
    • cites [180] source

      The Discussion says minesapride was well tolerated, and the Results > Safety identifies diarrhoea as the most common treatment-emergent adverse event. But the Results > Safety also reports tachycardia in a patient taking 40 mg, leading to discontinuation, so the statement that there were no cardiovascular adverse events is not supported. (LLM, conf=0.92)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Among individuals who believe themselves to have IBS, only around 60% fulfil Rome IV criteria, whereas 80% fulfil Rome III.

    “Among individuals who believe themselves to have IBS, only around 60% fulfil Rome IV criteria, whereas 80% fulfil Rome III.23”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Premisecitation

    Patients with IBS are at increased risk of iatrogenic harms, through unnecessary surgery, including hysterectomy, appendicectomy and cholecystectomy, and inappropriate prescribing of opioids.

    “Furthermore, patients are at increased risk of iatrogenic harms, through unnecessary surgery, including hysterectomy, appendicectomy and cholecystectomy, 121 and inappropriate prescribing of opioids.90”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [121] source
    • cites [90] Black, 2020, Functional gastrointestinal disorders: advances in understanding and management, The Lancet source

  • May combine two claims.

    Premisecitation

    Current treatments for IBS are often inadequate and many patients remain unsatisfied with medical care.

    “Current treatments for IBS are often inadequate and many patients remain unsatisfied with medical care.91 92 95”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [91] source
    • cites [92] Bertram, 2001, The patient’s perspective of irritable bowel syndrome, J Fam Pract
    • cites [95] source

  • May combine two claims.

    Premisecitation

    An RCT of delayed-release linaclotide, with action confined to the ileo-caecal region of the gastrointestinal tract, demonstrated significant effects on abdominal pain, with lower rates of diarrhoea than conventional-release linaclotide.

    “An RCT of delayed-release linaclotide, with action confined to the ileo-caecal region of the gastrointestinal tract, demonstrated significant effects on abdominal pain, with lower rates of diarrhoea than conventionrelease linaclotide.165”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [165] source

      The Introduction (page unavailable) says MD-7246 was designed to release at the ileocecal junction and cecum, but does not establish that its action was confined there. The Results (page unavailable) report modest abdominal-pain improvement with MD-7246, without a statistically significant effect versus placebo; the significant pain result was for DR1, which targets the ileum. The Safety results report lower diarrhea rates with MD-7246 than with immediate-release linaclotide. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S4 (based).

    Findingnone given

    Peppermint oil may be an effective treatment for global symptoms and abdominal pain in IBS.

    “Peppermint oil may be an effective treatment for global symptoms and abdominal pain in IBS.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Findingnone given

    Loperamide may be an effective treatment for diarrhoea in IBS.

    “Loperamide may be an effective treatment for diarrhoea in IBS.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Findingnone given

    Insoluble fibre (eg, wheat bran) should be avoided in IBS as it may exacerbate symptoms.

    “Soluble fibre, such as ispaghula, is an effective treatment for global symptoms and abdominal pain in IBS, but insoluble fibre (eg, wheat bran) should be avoided as it may exacerbate symptoms.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    Rifaximin is an efficacious second-line drug for IBS with diarrhoea in secondary care, although its effect on abdominal pain is limited.

    “The non-absorbable antibiotic rifaximin is an efficacious second-line drug for IBS with diarrhoea in secondary care, although its effect on abdominal pain is limited.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Studies do not distinguish between affective, cognitive and true peripheral, versus central, mechanisms of visceral hypersensitivity.

    “However, studies do not distinguish between affective, cognitive and true peripheral, versus central, mechanisms of visceral hypersensitivity.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    Tegaserod is an efficacious second-line drug for IBS with constipation in secondary care but is unavailable outside the USA.

    “Tegaserod, a 5-Hydroxytryptamine 4 receptor agonist, is an efficacious second-line drug for IBS with constipation in secondary care but is unavailable outside the USA.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Studies comparing the low FODMAP diet with traditional dietary advice from NICE and the BDA had the least heterogeneity, but also the least magnitude of effect (RR 0.82; 95% CI 0.67 to 1.01).

    “Interestingly, those studies that compared the low FODMAP diet with traditional dietary advice from NICE and the BDA had the least heterogeneity, but also the least magnitude of effect (RR 0.82; 95% CI 0.67 to 1.01), suggesting that the 50%-70% symptomatic benefit reported for a low FODMAP diet in some studies may have been overestimated.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    In one trial of polyethylene glycol, there was no significant effect on either abdominal pain or number of bowel movements, and in the second the number of bowel movements increased significantly, but with no improvement in abdominal pain.

    “In one trial, there was no significant effect on either abdominal pain or number of bowel movements, 221 and in the second the number of bowel movements increased significantly, but with no improvement in abdominal pain.222”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [221] source
    • cites [222] source

  • May combine two claims.

    Findingcitation

    Polyethylene glycol was generally well-tolerated with abdominal pain the most frequent adverse event.

    “Polyethylene glycol was generally well-tolerated with abdominal pain the most frequent adverse event.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [221] source
    • cites [222] source

  • May combine two claims.

    Findingcitation

    Blurred vision, dizziness and altered sensation were more common with pregabalin.

    “Blurred vision, dizziness and altered sensation were more common with pregabalin.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [228] source

  • May combine two claims.

    Findingcitation

    In a subsequent 'retreatment' trial, significantly more patients experienced an improvement in global symptoms with rifaximin after each treatment course, and there were no safety concerns.

    “In this RCT, patients received open-label rifaximin and were then randomised to two repeat 14-day courses of rifaximin or placebo if they experienced symptom relapse.Significantly more patients experienced an improvement in global symptoms with rifaximin after each treatment course, and there were no safety concerns.238”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [238] source

  • May combine two claims.

    Findingcitation

    A subsequent RCT of 12 mg once a day of bimodal release ondansetron also demonstrated superiority over placebo for improvement in stool consistency, but not abdominal pain.

    “A subsequent RCT of 12 mg once a day of bimodal release ondansetron also demonstrated superiority over placebo for improvement in stool consistency, but not abdominal pain.178”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [178] source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Each section lead performed a comprehensive literature search, except for the treatment section, which was informed by a systematic review of the literature.

    “Each section lead performed a comprehensive literature search, except for the section dealing with treatment, which was informed by a systematic review of the literature, the methodology for which is reported within that section.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisenone given

    In the absence of any biomarker for IBS, the condition is diagnosed using a positive approach based on the clinical history.

    “In the absence of any biomarker being available for IBS, the condition is diagnosed using a positive approach, based on the clinical history.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    The autonomic nervous system mediates communication between the gut and brain.

    “The autonomic nervous system mediates communication between the gut and brain.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    IBS is chronic, with fluctuating symptoms, in the majority of patients.

    “In the latter instance, IBS is chronic, with fluctuating symptoms, in the majority of patients.12”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] source

  • May combine two claims.

    Premisecitation

    In IBS, a reduction in parasympathetic activity and an increase in sympathetic nervous system activity is frequently observed.

    “In IBS, a reduction in parasympathetic activity and an increase in sympathetic nervous system activity is frequently observed.39”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [39] source

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    The vagus nerve may sense the gut microenvironment indirectly and transfer this information to the brain.

    “Conversely, the vagus nerve may sense the gut microenvironment indirectly and transfer this information to the brain.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Moving from Rome III to Rome IV IBS may reduce the likelihood of novel pharmacological therapies demonstrating efficacy in future randomised controlled trials, or may mean that trials need to be considerably larger and more expensive.

    “Moving from Rome III to Rome IV IBS may therefore reduce the likelihood of novel pharmacological therapies demonstrating efficacy in future randomised controlled trials (RCTs), due to the spectrum of symptom severity, or may mean that trials need to be considerably larger, and therefore more expensive to conduct, to show a beneficial effect.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The pathophysiology of IBS is complex and remains poorly understood.

    “The pathophysiology of IBS is complex and remains poorly understood. 2”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] source

  • May combine two claims.

    Premisereasoning

    In both meta-analyses of global IBS prevalence, heterogeneity between studies was substantial, presumably relating to differences in methodology, demographic characteristics of participants, cultural issues or a combination of these factors.

    “In both meta-analyses, heterogeneity between studies was substantial, presumably relating to differences in methodology, demographic characteristics of participants, cultural issues or a combination of these factors.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [11] source
    • cites [18] source

  • Classified as probably not a substantial claim.

    Premisecitation

    The presence of abdominal pain at the required frequency distinguishes IBS from other functional bowel disorders.

    “The presence of abdominal pain at the required frequency distinguishes IBS from the other functional bowel disorders, which consist of functional constipation, functional diarrhoea and functional abdominal bloating or distension. 2”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [2] source

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    The more restrictive nature of the Rome IV criteria calls into question whether they should be used to diagnose IBS in clinical practice.

    “This more restrictive nature of the Rome IV criteria calls into question whether they should be used to diagnose IBS in clinical practice, and a more pragmatic definition of the symptoms that constitute IBS may be preferred.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Colonic transit is abnormal in only 10%-20% of patients with IBS-C and IBS-M, and 25%-45% of patients with IBS-D.

    “Colonic transit is abnormal in only 10%-20% of patients with IBS-C and IBS-M, and 25%-45% of patients with IBS-D.44 45”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites 44 45

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim.

    Premisecitation

    Establishing an effective doctor-patient relationship and a shared understanding is key to the successful diagnosis and management of chronic conditions such as IBS.

    “Establishing an effective doctor-patient relationship and a shared understanding is key to the successful diagnosis and management of chronic conditions such as IBS.89 90”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites 89 90

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    The expression and levels of the tight junction protein zonula occludens are significantly reduced in IBS-D, and associated with mast cell activation and symptoms.

    “The expression and levels of the tight junction protein zonula occludens are significantly reduced in IBS-D, and associated with mast cell activation and symptoms.66”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [66] source

  • May combine two claims.

    Premisecitation

    The applicability of the Rome criteria to clinical practice has been challenged as unnecessarily restrictive, and only a minority of people diagnosed with IBS in primary care fulfil them.

    “Their applicability to clinical practice has been challenged as unnecessarily restrictive, 98 and only a minority of people diagnosed with IBS in primary care fulfil them.99”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [98] source
    • cites [99] source

  • May combine two claims.

    Premisecitation

    Increased permeability in patients with PI-IBS and IBS-D correlates with visceral sensitivity and symptom severity.

    “Increased permeability in patients with PI-IBS and IBS-D correlates with visceral sensitivity 60 61 and symptom severity.62 63”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites 60 61

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites 62 63

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Changes in the gut microbiome can modify gastrointestinal motility, visceral sensation, intestinal permeability, stool consistency and visceral sensitivity.

    “Moreover, changes in the gut microbiome can modify gastrointestinal motility, visceral sensation, intestinal permeability, stool consistency and visceral sensitivity.71 72”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites 71 72

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    The non-invasive marker of intestinal inflammation faecal calprotectin has enabled risk stratification to prioritise access to investigations to exclude IBD in patients with chronic diarrhoea, reducing unnecessary investigations and referrals from primary to secondary care.

    “The non-invasive marker of intestinal inflammation faecal calprotectin has enabled risk stratification to prioritise access to investigations to exclude IBD in patients with chronic diarrhoea, reducing unnecessary investigations and referrals from primary to secondary care.103”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [103] The new faecal calprotectin care pathway, 2018. Available: https://wwwniceorguk/sharedlearning/the-new-faecal-calprotectin-care-pathway

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The Rome criteria are the gold standard symptom-based diagnostic criteria for IBS.

    “the gold standard symptombased diagnostic criteria for IBS, the Rome criteria, are now in their fourth iteration.2”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] source

  • May combine two claims.

    Premisecitation

    The Rome diagnostic criteria are based on specific symptoms of a defined duration and frequency, which have been derived predominantly from secondary care patients, and are rarely used in primary care.

    “The Rome diagnostic criteria are based on specific symptoms of a defined duration and frequency, 2 which have been derived predominantly from secondary care patients, and are rarely used in primary care.97”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [2] source
    • cites [97] source

  • May combine two claims.

    Premisecitation

    Patients with IBS-C display reduced motility, fewer high amplitude propagating contractions of the colon and delayed transit, whereas those with IBS-D have increased motility, more high amplitude propagating contractions and accelerated transit.

    “Patients with IBS-C display reduced motility, fewer high amplitude propagating contractions of the colon and delayed transit, whereas those with IBS-D have increased motility, more high amplitude propagating contractions and accelerated transit. 1”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] source

  • May combine two claims.

    Premisecitation

    Patients with IBS often feel their symptoms are dismissed or trivialised, describe the diagnostic process as confusing, or invasive, and the often-lengthy search for efficacious treatments as frustrating.

    “They often feel their symptoms are dismissed or trivialised, describe the diagnostic process as confusing, or invasive, and the often-lengthy search for efficacious treatments as frustrating.87 89 91 -95”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites 87 89 91 -95

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Most patients with IBS are keen to explore dietary options, with over 60% wanting to know what food(s) they should avoid, and up to 70% having modified their diet.

    “Hence, most patients with IBS are keen to explore dietary options, with over 60% wanting to know what food(s) they should avoid, and up to 70% having modified their diet.192”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [192] source

  • May combine two claims.

    Premisecitation

    Coexistent early satiety, postprandial fullness, epigastric pain, nausea or heartburn are common, as functional dyspepsia and gastro-oesophageal reflux frequently overlap with IBS.

    “Coexistent early satiety, postprandial fullness, epigastric pain, nausea or heartburn are common, as functional dyspepsia and gastro-oesophageal reflux frequently overlap with IBS.[115][116][117]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [115][116][117]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Extraintestinal symptoms, such as back pain, bladder and gynaecological symptoms, and insomnia are frequent, as is the presence of other functional somatic disorders, such as fibromyalgia, tension headache or chronic fatigue.

    “Extraintestinal symptoms, such as back pain, bladder and gynaecological symptoms, and insomnia are frequent, as is the presence of other functional somatic disorders, such as fibromyalgia, tension headache or chronic fatigue.118”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [118] Petersen, 2020, The unifying diagnostic construct of bodily distress syndrome (BDS) was confirmed in the general population, J Psychosom Res source

  • May combine two claims.

    Premisecitation

    IBS is not associated with an increased risk of cancer or mortality, but affects quality of life to the same degree as organic gastrointestinal diseases, such as IBD.

    “IBS is not associated with an increased risk of cancer or mortality, 149 but affects quality of life to the same degree as organic gastrointestinal diseases, such as IBD. 13”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [149] source
    • cites [13] source

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Local laboratory values vary but, generally, a faecal calprotectin of <100 μg/g can be considered normal, 100-249 μg/g is borderline and should be repeated, with subsequent referral if persistently elevated, and ≥250 μg/g requires urgent referral to secondary care to exclude IBD.

    “Local laboratory values vary but, generally, a faecal calprotectin of <100 μg/g can be considered normal, 100-249 μg/g is borderline and should be repeated, with subsequent referral if persistently elevated, and ≥250 μg/g requires urgent referral to secondary care to exclude IBD.103”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [103] The new faecal calprotectin care pathway, 2018. Available: https://wwwniceorguk/sharedlearning/the-new-faecal-calprotectin-care-pathway

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Factors that should alert the clinician to the possibility of microscopic colitis include female sex, age ≥50 years, coexistent autoimmune disease, nocturnal or severe, watery, diarrhoea, duration of diarrhoea <12 months, weight loss or use of potential precipitating drugs including NSAIDs, PPIs, selective serotonin reuptake inhibitors (SSRIs) or statins.

    “Factors that should alert the clinician to the possibility of microscopic colitis include female sex, age ≥50 years, coexistent autoimmune disease, nocturnal or severe, watery, diarrhoea, duration of diarrhoea <12 months, weight loss or use of potential precipitating drugs including NSAIDs, PPIs, selective serotonin reuptake inhibitors (SSRIs) or statins.[127][128][129]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [127][128][129]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Study design and conductreasoning

    Most trials recruited unselected patients with IBS, so whether the proposed reduction in gastrointestinal motility with antispasmodics improves diarrhoea is unclear.

    “In addition, most trials recruited unselected patients with IBS, so whether the proposed reduc- tion in gastrointestinal motility with antispasmodics improves diarrhoea is unclear.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    These findings should be interpreted with caution, given heterogeneity between trial results and the varying end points studied.

    “However, these findings should be interpreted with caution, given heterogeneity between trial results and the varying end points studied.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductreasoning

    Low study quality, the lack of consistent use of the Rome criteria to define IBS and heterogeneity between RCTs limit confidence in the data on peppermint oil.

    “In addition, low study quality, the lack of consistent use of the Rome criteria to define IBS and heterogeneity between RCTs limit confidence in the data.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Peppermint oil's putative antispasmodic action is via L-menthol's blockade of calcium channels.

    “Although not completely understood, its putative antispasmodic action is via L-menthol's blockade of calcium channels.218”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [218] source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Current NICE guidance for the management of IBS suggests that patients with IBS-C can be treated with laxatives, advising dose titration according to symptoms.

    “Current NICE guidance for the management of IBS suggests that patients with IBS-C can be treated with laxatives, advising dose titration according to symptoms.10”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] source

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    Loperamide is a synthetic μ-opioid agonist that reduces myenteric plexus activity, thereby increasing intestinal transit time and enhancing water reabsorption.

    “Loperamide is a synthetic μ-opioid agonist that reduces myenteric plexus activity, thereby increasing intestinal transit time and enhancing water reabsorption.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    The long-term efficacy of osmotic laxatives in IBS-C is unknown, as both trials were of only 4 weeks duration.

    “The long-term efficacy of osmotic laxatives in IBS-C is unknown, as both trials were of only 4 weeks duration.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    It is not possible to recommend a specific species or strain of probiotic.

    “Probiotics, as a group, may be an effective treatment for global symptoms and abdominal pain in IBS, but it is not possible to recommend a specific species or strain.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Due to the modest efficacy, and concerns over the potential for adverse events (including Clostridium difficile infection and bacterial resistance) with repeated courses of rifaximin, FDA approval was not forthcoming.

    “Due to the modest efficacy, and concerns over the potential for adverse events (including Clostridium difficile infection and bacterial resistance) with repeated courses of rifaximin, FDA approval was not forthcoming.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Patients with IBS often have comorbid anxiety and depression, and these are also risk factors for the subsequent development of IBS in healthy people.

    “Patients with IBS often have comorbid anxiety and depression, 119 and these are also risk factors for the subsequent development of IBS in healthy people.31”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [119] source
    • cites [31] source

  • May combine two claims.

    Premisecitation

    There have been no RCTs of SNRIs in IBS, although there is evidence from case series that duloxetine may improve symptoms and quality of life, and there is good evidence for use of SNRIs in other chronic painful disorders, such as fibromyalgia and low back pain.

    “There have been no RCTs of SNRIs in IBS, although there is evidence from case series that duloxetine may improve symptoms and quality of life, 224 225 and there is good evidence for use of SNRIs in other chronic painful disorders, such as fibromyalgia and low back pain.226”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [224] source
    • cites [225] source
    • cites [226] source

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    Although licensed for IBS-D, eluxadoline is unavailable in many countries.

    “Although licensed for IBS-D, the drug is unavailable in many countries.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    The drug is now licensed for IBS-D in the USA but is not available for this indication in many countries.

    “The drug is now licensed for IBS-D in the USA but is not available for this indication in many countries.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    It is likely that these approaches have similar efficacy, but more work is needed to determine cost-effectiveness of the various modes of delivery.

    “It is likely that these approaches have similar efficacy, but more work is needed to determine cost-effectiveness of the various modes of delivery.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In one European study, approximately one in four individuals with IBS were categorised as severe in a general population setting.

    “In one European study, approximately one in four individuals with IBS were categorised as severe in a general population setting.266”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [266] Manzoli, 2017, Prevalence of severe irritable bowel syndrome among Italian adults, A meta-analysis. Eur Rev Med Pharmacol Sci source

  • May combine two claims.

    Premisecitation

    Diarrhoea was the most common adverse event with tegaserod and was significantly more likely than with placebo.

    “Diarrhoea was the most common adverse event and was significantly more likely than with placebo.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [163] source

  • May combine two claims.

    Premisecitation

    The risk of missing, or subsequently developing, an organic disorder in patients diagnosed with IBS is low, but this rate may be increased in those with severe symptoms.

    “Although the risk of missing, or subsequently developing, an organic disorder in patients diagnosed with IBS is low, this rate may be increased in those with severe symptoms, 267”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [267] source

  • May combine two claims.

    Interpretationreasoning

    These data suggest that treatment with IBS-specific CBT protocols may benefit both mental health and gastrointestinal symptoms.

    “These data suggest that treatment with IBS-specific CBT protocols may benefit both mental health and gastrointestinal symptoms.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    There were also significant improvements in extraintestinal symptoms, and anxiety and depression scores with hypnotherapy.

    “There were also significant improvements in extraintestinal symptoms, and anxiety and depression scores.252”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [252] source

  • May combine two claims.

    Interpretationreasoning

    Evidence suggests that CBT for IBS is effective in both high-intensity (therapist-delivered) and minimal contact (therapist-guided) formats, as well as self-administered with either bibliographic material or web-based.

    “Evidence suggests, therefore, that CBT for IBS is effective in both high-intensity (therapist-delivered) and minimal contact (therapist-guided) formats, as well as self-administered with either bibliographic material or web-based.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The cannabinoid type-2 receptor agonist olorinab has been tested in patients with quiescent Crohn's disease, and led to reductions in abdominal pain and improved bowel movements.

    “The cannabinoid type-2 receptor agonist, olorinab, has been tested in patients with quiescent Crohn's disease, and led to reductions in abdominal pain and improved bowel movements 293”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [293] Yacyshyn, 2019, Su1930 – Safety and Efficacy of Olorinab, a Peripherally Restricted, Highly Selective, Cannabinoid Receptor 2 Agonist in a Phase 2A Study in Chronic Abdominal Pain Associated with Crohn’s Disease, Gastroenterology source

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationreasoning

    Emphasising a more pragmatic clinical definition of IBS, together with limited need for investigations, would allow faster recruitment to RCTs, provide equity of access for patients and give a better indication of the true benefit of treatments being studied in the population most likely to use them.

    “This would allow faster recruitment to RCTs, provide equity of access for patients and give a better indication of the true benefit of treatments being studied in the population most likely to use them.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: There are often severity criteria built in, which aim to exclude the most severe or refractory symptoms, as well as less severe cases.
    • Rests on an assumption: Many treatments are restricted to patients with IBS-C or IBS-D, whereas those with IBS-M or IBS-U are rarely recruited.
    • Rests on an assumption: Although there are established composite end points for IBS-C and IBS-D, these do not exist for IBS-M or IBS-U.
    • Rests on an assumption: Recruitment to trials is optimal when patients are linked to specialist clinics.
    • Rests on an assumption: Patients with IBS are widely disseminated, mostly in community care, often with no long-term follow-up, and only a minority attend specialist clinics where research is undertaken.
    • Rests on an assumption: The latter group (specialist clinic patients) is often more complex, more refractory and, by definition, less appropriate for treatment trials.
    • Rests on an assumption: There are often too many visits, a need for invasive investigations, and a high burden of data collection.
    • Rests on an assumption: Patients who enter IBS trials have usually tried all available treatments and remain unsatisfied with care, so being randomised to 'standard care' for ≥12 weeks is unappealing.

  • May combine two claims.

    Premisecitation

    In most patients a diagnosis of IBS is secure, and further repeated investigations have a low yield.

    “Nevertheless, it is important to stress that in most patients a diagnosis of IBS is secure, 111 and further repeated investigations have a low yield.268”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [111] source
    • cites [268] source

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationnone given

    Although RCTs remain the gold standard, they have many weaknesses, and modern methods of trial design may be more suitable to studying IBS.

    “Although RCTs remain the gold standard, they have many weaknesses, and modern methods of trial design may be more suitable to studying IBS.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: There are often severity criteria built in, which aim to exclude the most severe or refractory symptoms, as well as less severe cases.
    • Rests on an assumption: Many treatments are restricted to patients with IBS-C or IBS-D, whereas those with IBS-M or IBS-U are rarely recruited.
    • Rests on an assumption: Although there are established composite end points for IBS-C and IBS-D, these do not exist for IBS-M or IBS-U.
    • Rests on an assumption: Recruitment to trials is optimal when patients are linked to specialist clinics.
    • Rests on an assumption: Patients with IBS are widely disseminated, mostly in community care, often with no long-term follow-up, and only a minority attend specialist clinics where research is undertaken.
    • Rests on an assumption: The latter group (specialist clinic patients) is often more complex, more refractory and, by definition, less appropriate for treatment trials.
    • Rests on an assumption: There are often too many visits, a need for invasive investigations, and a high burden of data collection.
    • Rests on an assumption: Patients who enter IBS trials have usually tried all available treatments and remain unsatisfied with care, so being randomised to 'standard care' for ≥12 weeks is unappealing.

  • May combine two claims.

    Interpretationreasoning

    Despite the high prevalence of IBS, the pipeline of new treatments is relatively poor.

    “Despite this, and the high prevalence of IBS, the pipeline of new treatments is relatively poor.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    IBS is a multifactorial disorder of gut-brain interaction.

    “is a multifactorial disorder of gut-brain interaction”
    Quote in the paperNot a substantial claim
141 of 141

  • The paper relies on this without support.

    The evidence from clinical trials and meta-analyses is applicable to the general IBS population in clinical practice.

    “The primary aim of this guideline, commissioned by the BSG, is to review and summarise the current evidence to inform and guide clinical practice, by providing a practical framework for evidence-based management of patients.”

  • The paper relies on this without support.

    The recommendations will lead to improved patient outcomes.

    “providing a practical framework for evidence-based management of patients.”

  • The paper relies on this without support.

    The quality of evidence grading accurately reflects the certainty of the evidence.

    “Specific recommendations have been made according to the Grading of Recommendations Assessment, Development and Evaluation system, summarising both the strength of the recommendations and the overall quality of evidence.”

  • The paper relies on this without support.

    The main pathophysiological aspect of IBS is related to visceral hypersensitivity, which is also the principal target of many current treatments.

    “The main pathophysiological aspect is related to visceral hypersensitivity, which is also the principal target of many current treatments.”

  • The paper relies on this without support.

    IBS is a disorder of gut-brain interaction.

    “explaining IBS as a disorder of gut-brain interaction”

  • The paper relies on this without support.

    Cure is unlikely, but substantial improvement in symptoms, social functioning and quality of life is achievable.

    “It is important to stress that cure is unlikely, but substantial improvement in symptoms, social functioning and quality of life is achievable.”

  • The paper relies on this without support.

    Most second-line drugs are only available in secondary care.

    “Most second-line drugs are only available in secondary care.”

  • The paper relies on this without support.

    The treatment of IBS is generally directed towards the predominant symptom, or symptoms, experienced by the patient.

    “The treatment of IBS is generally directed towards the predominant symptom, or symptoms, experienced by the patient.”

  • The paper relies on this without support.

    Calprotectin is not specific to IBD and can be elevated in older age groups (age ≥45 years), obesity, infection, malignancy or by medications, such as proton pump inhibitors (PPIs) or non-steroidal anti-inflammatory drugs (NSAIDs).

    “However, calprotectin is not specific to IBD and can be elevated in older age groups (age ≥45 years), obesity, infection, malignancy or by medications, such as proton pump inhibitors (PPIs) or non-steroidal anti-inflammatory drugs (NSAIDs).”

  • The paper relies on this without support.

    The Rome IV criteria are the gold standard to define IBS for research purposes.

    “Although the Rome IV criteria are the gold standard to define IBS for research purposes”

  • The authors state this as an assumption.

    Some IBS symptoms are a result of gastrointestinal spasm and dysmotility, which antispasmodics ameliorate.

    “The proposed mechanism of action of these agents is based on the assumption that some IBS symptoms are a result of gastrointestinal spasm and dysmotility, which antispasmodics ameliorate.217”

  • The paper relies on this without support.

    In clinical practice, abdominal pain, bloating, nausea and constipation are common side effects of loperamide, and may limit tolerability.

    “However, in clinical practice, abdominal pain, bloating, nausea and constipation are common side effects, and may limit tolerability.”

  • The paper relies on this without support.

    Dysfunction within the bidirectional gut-brain axis plays an important role in the genesis and maintenance of symptoms in IBS.

    “Dysfunction within the bidirectional gut-brain axis is considered to play an important role in the genesis and maintenance of symptoms in IBS.”

  • The paper relies on this without support.

    There are often severity criteria built in, which aim to exclude the most severe or refractory symptoms, as well as less severe cases.

    “There are often severity criteria built in, which aim to exclude the most severe or refractory symptoms, as well as less severe cases.”

  • The paper relies on this without support.

    Many treatments are restricted to patients with IBS-C or IBS-D, whereas those with IBS-M or IBS-U are rarely recruited.

    “many treatments are restricted to patients with IBS-C or IBS-D, whereas those with IBS-M or IBS-U are rarely recruited”

  • The paper relies on this without support.

    Although there are established composite end points for IBS-C and IBS-D, these do not exist for IBS-M or IBS-U.

    “although there are established composite end points for IBS-C and IBS-D, these do not exist for IBS-M or IBS-U”

  • The paper relies on this without support.

    Recruitment to trials is optimal when patients are linked to specialist clinics.

    “Second, recruitment to trials is optimal when patients are linked to specialist clinics.”

  • The paper relies on this without support.

    Patients with IBS are widely disseminated, mostly in community care, often with no long-term follow-up, and only a minority attend specialist clinics where research is undertaken.

    “However, patients with IBS are widely disseminated, mostly in community care, often with no long-term follow-up, and only a minority attend specialist clinics where research is undertaken.”

  • The paper relies on this without support.

    The latter group (specialist clinic patients) is often more complex, more refractory and, by definition, less appropriate for treatment trials.

    “This latter group is often more complex, more refractory and, by definition, less appropriate for treatment trials.”

  • The paper relies on this without support.

    There are often too many visits, a need for invasive investigations, and a high burden of data collection.

    “There are often too many visits, a need for invasive investigations, and a high burden of data collection.”

  • The paper relies on this without support.

    Patients who enter IBS trials have usually tried all available treatments and remain unsatisfied with care, so being randomised to 'standard care' for ≥12 weeks is unappealing.

    “Patients who enter IBS trials have usually tried all available treatments and remain unsatisfied with care, so being randomised to 'standard care' for ≥12 weeks is unappealing.”
21 of 21

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Some probiotics may be beneficial in irritable bowel syndrome (IBS).

    “Some probiotics may be bene fi cial in irritable bowel syndrome (IBS), but differences in species and strains used, as well as endpoints reported, have hampered attempts to make speci fi c recommendations as to which should be preferred.”

    From Efficacy of Probiotics in Irritable Bowel Syndrome: Systematic Review and Meta-analysis (2023) · cites this paper as [10]

    The Probiotics section reports significant improvements in global symptoms or abdominal pain for several probiotic groups and says variation in strains, species, and study design makes specific recommendations difficult. It does not specifically identify differences in reported endpoints as a reason recommendations are difficult. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

Cites

Flagged first, then by citations

Research works printed but not linked: 3

  1. Howick J , Phillips B , Ball C . Oxford centre for evidence-based medicine levels of evidence. University of Oxford, Centre for Evidence-Based Medicine, 2009.
  2. National Institute for Health and Care Excellence . Suspected cancer: recognition and referral NICE guideline [NG12], 2015. Available: https://wwwniceorguk/guidance/ng12/chapter/1-recommendations-organised-by-site-of-cancer#lower-gastrointestinal-tract-cancers
  3. Zhang Y , Fox M , Dai N . Low-FODMAP diet versus traditional dietary advice for diarrhea-predominant irritable bowel syndrome: a randomized, parallel-controlled trial with analysis of clinical and microbiological factors associated with patient outcome. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society 2020;32.

Cited by

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Related

Authors
Vasant, D. H., Paine, P. A., Black, C. J., Houghton, L. A., Everitt, H. A., Corsetti, M., Agrawal, A., Aziz, I., Farmer, A. D., Eugenicos, M. P., Moss-Morris, R., Yiannakou, Y., & Ford, A. C.
Affiliations
  • University of Manchester (GB)
  • Salford Royal NHS Foundation Trust (GB)
  • University of Leeds (GB)
  • University of Southampton (GB)
  • University of Nottingham (GB)
  • Bassetlaw Hospital (GB)
  • Sheffield Teaching Hospitals NHS Foundation Trust (GB)
  • University Hospitals of North Midlands NHS Trust (GB)
  • Western General Hospital (GB)
  • King's College London (GB)
  • National Health Service (GB)
Corresponding author
Ford, Alexander C
ORCID
Venue
Gut
Publisher
BMJ
Published
2021-04-26
Volume
70
Issue
7
Pages
1214-1240
ISSN
  • 0017-5749 (ISSN-L)
  • 1468-3288
DOI
10.1136/gutjnl-2021-324598
OpenAlex
W3159143441
Cited by
547
References
309
Citations by year
2026: 104 · 2025: 123 · 2024: 98 · 2023: 105 · 2022: 81 · 2021: 26
FWCI
50.45
Type
journal article
Language
en
Open access
Locations
  • Gut (publishedVersion)
  • PubMed (publishedVersion)
  • ePrints Soton (University of Southampton) (acceptedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (submittedVersion)
  • Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by-nc)
  • Research Explorer (The University of Manchester) (submittedVersion)
Topics
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Health Sciences › Medicine › Complementary and alternative medicine › Complementary and Alternative Medicine Studies
  • Health Sciences › Medicine › Physiology › Diet and metabolism studies
Keywords
irritable bowel syndrome, gut-brain axis, IBS diagnosis, IBS management, dietary therapy, pharmacotherapy, psychotherapy, network meta-analysis
MeSH terms
Drug Development, Communication, Constipation, Diarrhea, Diet, United Kingdom, Humans

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-11.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-11.

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Statistics and arithmetic are recomputed, not judged.

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